Chronic obstructive pulmonary disease (COPD) is characterized by the progressive development of airflow limitation (airway obstruction) (Pauwell R. A., et al.: Am. J. Respir. Crit. Care Med., 2001 (163), 1256-1276).
COPD is one of the major causes of chronic morbidity and mortality throughout the world, and in the Asia-Pacific region, it is also foreseen that patients of COPD will rapidly increase within about 20 years from now on, due to the growth of smokers and the aging population.
A diagnosis of COPD should be considered in smokers who have clinical symptoms and signs, such as progressive developing abnormal shortness of breath, associated with airflow obstruction. For this reason, every country in the world has been paying much attention to diagnosis and treatments of COPD.
At present, as to drug therapy for the treatment of COPD, certain drugs such as β2-stimulants, anticholinergic agents and the like, having bronchodilatory action are tentatively used for preventing or suppressing the symptoms. However, these drugs having bronchodilatory action cannot exhibit an improvement in deterioration of the pulmonary function for long period of time, which is the characteristic of COPD and the most important clinical index.
Regarding the effect of steroids, having potent inhibitory effect on the production of cytokines, as an inhalant have been assessed in plural clinical studies in large scale. However, most of them also showed that steroids could not improve the deterioration of the pulmonary function for long period of time (Pauwels R. A., Lodahl C. G., Laitinen L. A., Schouten J. P., Postma D. S., Pride N. B., et al: N. Engl. J. Med., 1999 (340), 1948-1953; Vestbo J., Sorensen T., Lange P., Brix A., Torre P., Viskum K.: Lancet, 1999 (353), 1819-1823; Burge P. S., Calverley P. M., Jones P. W., Spencer S., Anderson J. A., Maslen T. K.: BMJ, 2000 (320), 1297-1303)).
Regarding the drugs having inhibitory effect on the production of active oxygen, any reliable clinical studies have not been examined as yet.
N-acetylcystein is an antioxidant having a similar effect to that of agents having inhibitory action on the production of active oxygen. While, clinical study showed that N-acetylcystein could reduce the acute exacerbation rate of COPD (C. Stey, J. Steure, S. Bachmann, T. C. Medici, M. R. Tramer; Eur. Respir. J., 2000, (16), 253-262). However, there are no reports at all, that N-acetylcystein shows to improve the deterioration of the pulmonary function in COPD patients for long period of time.
Furthermore, clinical studies are conducting to examine whether the drugs inhibiting phosphodiesterase IV activity will be the treatment of COED. However, it has been reported that these drugs have adverse side-effects as well, for example, nausia, vomiting and increasing the secretion of acid in the stomach (Peter J. Barnes: N. Engl. J. Med., 2000 (343) No. 4, 269-280).
As is explained above, there are no drugs having improvement in deterioration of the pulmonary function in CCPD, as well as having sufficient ability as a drug for the treatment of COPD, which have yet been developed.